The pharmaceutical industry develops a variety of products that require approval from the FDA often based on measurements derived from medical images. One of the most expensive and time-consuming aspects of drug development relates to clinical trials for getting anticancer agents such as anticancer drugs approved. This is particularly evident in the field of oncology, although it is also applicable to other medical fields.
In the field of oncology, the use of medical images for assessing response to an anticancer agent treatment is now commonplace. Many clinical trials use measurements of variations in the size of an abnormality or lesion, such as a tumor, as the prime indicator of treatment effect. Although change in patient survival is considered a primary endpoint, along with others, in making the evaluation of drug effectiveness, this metric, by necessity, is evaluated less frequently than the surrogate endpoint of change in tumor size as a means of receiving FDA approval. For example, a drug used to treat lung cancer might be evaluated using criteria based on the rate of reduction in size of a tumor or other lesion in the lung.
RECIST (Response Evaluation Criteria In Solid Tumors) criterion is a formal method that has been established to measure change in tumor size. RECIST comprises a set of published rules that define when cancer patients improve (“respond”), stay the same (“stable”), or worsen (“progression”) during treatments. The criteria were published by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute (NCI) of the United States, and the National Cancer Institute of Canada Clinical Trials Group. (See Therasse, et al., “New Guidelines to Evaluate the Response to Treatment in Solid Tumors,” Journal of the National Cancer Institute, Vol. 92, No. 3, Feb. 2, 2000, 205-216.) Today, the majority of clinical trials evaluating cancer treatments for objective response in solid tumors are using RECIST.
The essence of the RECIST criterion is the use of a single dimensional measurement wherein an image containing the largest cross-sectional diameter of the tumor is selected and the largest measurement in one dimension is obtained from that image. The one dimensional measurement is then compared at a specific time to a comparable image of the same tumor to assess for response. According to RECIST, complete response is defined as disappearance of the tumor, partial response is defined as a 30% decrease in size, and progression is defined as greater than a 20% increase in tumor size. RECIST does not consider lesions smaller than 1 cm.
In taking any measurement, accuracy is a critical issue. Unfortunately, the current RECIST approach for assessment of tumor response to treatment is severely limited because it does not consider measurement accuracy. As a result, it suffers from the need to observe large changes in single dimensional measurements in order to determine if there has been a response to treatment. The need for such large changes relates to an inability to reliably make measurements of a tumor size.
In previous standard practice, caliper measurements made by radiologists have been used to measure tumor size. The accuracy of measurements has been estimated by measuring variability of expert radiologists in measuring either phantom or actual nodules. Errors related to manually measuring tumor lengths can be quite large. Similarly, the inability to reliably select comparable imaging planes on temporally separated scans necessitates reliance on large changes in order to be certain that the change is genuine and not one of measurement error.
Other systems, such as presented in Kaufman et al., U.S. Pub. No. US 2003/0016850 A1, published Jan. 23, 2003 only compare two superimposed images. However, methods for accurate measurement evaluation including, among others, determining a bound on the error of a size change measurement are lacking.
Generally, current methods do not offer a process for accurate measurement evaluation having steps in accordance with the present invention that use volumetric methods for size determination. Current methods measure the extent of the tumor in one slice and in only one or two directions, rather than measuring all voxels associated with the tumor.